In vitro activity of rilopirox against fluconazole-susceptible and fluconazole-resistant Candida isolates from patients with HIV infection

The in vitro antifungal activity of the new hydroxypyridone antimycotic ril opirox has been evaluated against 38 fluconazole-susceptible and -resistant clinical isolates of Candida albicans together with other Candida species isolated from patients with human immunodeficiency virus (HIV) infection an d oropharyngeal candidosis. Minimum inhibitory concentrations (MICs) of bot h rilopirox and fluconazole were measured by a microdilution method using h igh-resolution medium supplemented with asparagine and glucose at pH 7.0. I n comparison, an agar dilution technique was carried out for susceptibility testing of the antifungal agents, Rilopirox was found to be able to inhibi t growth of all clinical yeast isolates. The rilopirox MICs at which 50% an d 90% of strains were inhibited (MIC50 and MIC90 respectively), as determin ed by the microdilution method, were 4 and 8 mu g ml(-1) respectively. The highest MIC values for rilopirox using microdilution and the agar dilution method were 32 or 25 mu g ml(-1) respectively. On the other hand, for fluco nazolc, the MIC50 and MIC90 achieved were 0.5 and 128 mu g ml(-1), respecti vely, which means that the MIC90 value of fluconazole was 16-fold higher th an that of rilopirox. Using the agar dilution technique, the MIC values of rilopirox were in the range 0.006-25 mu g ml(-1) with a median of 3.12 mu g ml(-1). For fluconazolc, the MIC90 value was four-fold higher than that fo r rilopirox, indicating a considerable proportion of yeast strains with hig h MICs of 100 mu g ml(-1), suggesting in vitro resistance to this azole ant ifungal. All strains with diminished fluconazole susceptibility were suscep tible to rilopirox. Even Candida krusei and Candida glabrata exhibited good in vitro susceptibility to rilopirox. Therefore, this new antifungal agent may be used as an alternative not only in the treatment of vaginal candido sis, but also in oropharyngeal Candida infections, e.g. in AIDS patients.